The State Department confirmed that one of those killed and five of the 178 people injured were U.S. citizens, CNN reported. About 95 people of the 218 passengers were still hospitalized.
The accident occurred at 8:41 p.m. Wednesday, about an hour before sunset, in the cathedral city of Santiago de Compostela in the northwest region of Galicia.
Police in Galicia said the driver was being held for questioning but had not been formally charged, CNN said.
The 13-car, nearly new, hybrid diesel-electric train emerged from a tunnel at about 120 mph and derailed on a sharp curve where the speed limit was 50 mph, Spanish newspaper El Pais reported.
Prime Minister Mariano Rajoy cleared his schedule to tour the scene, and offer support to injured victims and families of the dead and injured, ThinkSpain reported. King Juan Carlos and his family canceled all events for Thursday.
President Obama said he and his wife, Michelle, were "shocked and saddened" by the news.
"On behalf of the American people, we offer our deepest sympathies and condolences to the families and loved ones of the more than 80 people who lost their lives," he said. "We extend our wishes for a full recovery to those who were hurt."
Health officials issued an urgent appeal for blood. Thursday is a public holiday in Galicia and local officials canceled regional festivities, ThinkSpain reported.
"I want to express my affection and solidarity with the victims of the terrible train accident," Rajoy said on Twitter. He said he was "devastated" by the high-speed crash.
The derailment about 2.5 miles from the Santiago train station sent cars flying and rolling over on their sides.
Bodies, some in pieces, were covered by blankets next to the tracks as rescue workers tried to get trapped people out of the train's cars. Some people were pulled out of broken windows.
Images showed one train car pointed up into the air with one of its ends twisted out of shape. Another car, severed in two, was lying on a road nearby.
At least one car caught fire.
"Help came in 5 minutes but that time was eternal," Oscar Mateos, a police officer who was a passenger in the first car, told El Pais. "I helped out people with broken legs and many bruises."
The train, en route from Madrid, was scheduled to end its journey at El Ferrol, an Atlantic coastal city about 60 miles north of Santiago de Compostela.
The train wasn't one of Spain's highest speed bullet trains, called AVEs, though it was using the same type of track as Spain's fastest expresses, which can go nearly 200 mph.
The route had been renovated to suit the high-speed trains, but the signaling system had yet to be updated, El Pais said.
An engineer for state-owned ADIF -- which manages most of Spain's railway infrastructure, including tracks, signaling and stations -- told the newspaper while speeding contributed to the accident, some other cause must also have been involved.
He didn't say what he thought the other cause was.
ADIF and state-owned train operator Renfe Operadora promised to cooperate with a judge appointed to investigate the accident.